Process for the preparation of enantiomerically pure pyrethroid insecticides

ABSTRACT

A process for producing compounds of formula (VIIa) and (VIIb) wherein X is a leaving group; Y and Y 1  are idependently Cl or Br; and Z is Cl, Br or a haloalkyl group which process comprises a) reacting a compound of formula (VII) wherein X, Y, Y 1  and Z are as defined for compounds (VIIa) and (VIIb) with a substantially optically pure chiral amine in a solvent to form a diastereoisomeric salt; b) separating the diastereomeric salt of each enantiomer; c) converting the diastercomeric salt of each anantiomer separately to compounds of formulae (VIIa) and (VIIb) respectively by acid or base hydrolysis, the use of the compounds in making pyrethroid insecticides and novel intermediates.

[0001] The present invention relates to a process for makingcyclopropanecarboxylic acid esters, to intermediates used in the processand their use in making insecticides and acaricides.

[0002] Cyclopropanecarboxylic acids are useful in the synthesis ofpyrethroid insecticides and acaricides. Particularly importantpyrethroid intermediates are compounds of formula (III).

[0003] wherein Y is Cl or Br and Z is Cl, Br or a haloalkyl group.

[0004] Compounds of formula (III) may, as discussed below, be convertedto certain compounds of formula (I):

[0005] wherein Y is Cl or Br and Z is Cl, Br or a haloalkyl group and Eis an insecticidally active ester moiety such as those derived from4-alkyltetrafluorobenzyl alcohols (especially 4-methyltetrafluorobenzylalcohol), 4-alkoxytetrafluorobenzyl alcohols, α-cyano-3-phenoxybenzylalcohol, 3-phenoxybenzyl alcohol and 2-methyl-3-phenylbenzyl alcohol.

[0006] It will be appreciated by those skilled in the art that compoundsof formula (III) can exist in several stereoisomeric forms. If X and Yare different, there are a total of 3 stereocentres leading to a totalof 8 possible stereoisomers. Four of these isomers have the cisstereochemistry about the cyclopropane ring and four of them are trans.Esters of cis-3-(haloalkenyl)-2,2-dimethylcyclopropanecarboxylic acid offormula (III) with for example 4-alkyltetrafluorobenzyl alcohols(especially 4-methyltetrafluorobenzyl alcohol),4-alkoxytetrafluorobenzyl alcohols, α-cyano-3-phenoxybenzyl alcohol,3-phenoxybenzyl alcohol and 2-methyl-3-phenylbenzyl alcohol areimportant insecticidal and acaricidal products, and these acids areimportant intermediates in the manufacture of such products. When Y andZ are different, each cis form of the compound of the formula (III) iscomprised of two geometrical isomers, named Z and E isomers and it isthe Z isomer that is desirable when Y═Cl and Z is haloalkyl.Furthermore, when Y and Z are different, each cis-Z form of the compoundof the formula (III) is comprised of two enantiomers, sometimes referredto as optical isomers and usually described in terms of the direction inwhich they rotate plane polarised light, either (+) or (−). Alternativenomenclature is based on the absolute configuration of the C1 positionof the cyclopropane ring, either 1R or 1S. The most desirableenantiomers of pyrethroids acids are the cis 1R (+) enantiomers as thesehave superior insecticidal activity. However, other enantiomers may alsobe used to make highly active insecticides such as 1R trans Scypermethrin (i.e. Y═Z═Cl) (WO97/14308 and J. Environ. Sci. Health, PartB (1996), B31(3), 527). It is therefore desirable to manufacture certainpyrethroid products as single enantiomers or in enantiomericallyenriched form.

[0007] The manufacture of single enantiomers or enantiomericallyenriched products on an industrial scale is a very complex procedure.One approach to the synthesis of single enantiomer or enantiomericallyenriched products is to use intermediates which contain the desiredstereochemistry. For example to make the compounds of formula I′ below(containing 3 asymmetric carbon atoms as indicated by an *) thesynthesis could use enantiomeric forms or enantiomerically enrichedforms of compounds of formula (II), (III), (IV), (V), (VI) or (VII) asshown, wherein X is a leaving group such as Cl or Br; Y and Y¹ areindependently Cl or Br; Z is Cl, Br or a haloalkyl group and R is H oran alkyl group.

[0008] Enantiomeric forms or enantiomerically enriched forms ofcompounds (II), (III), (IV), (V), (VI) or (VII) are not availablecommercially and it is therefore desirable to find a process to resolveone of the above racemic compounds. It is preferable to introduce theresolution of enantiomers as early as possible in the synthetic process(for cost and output reasons). Thus in the process shown in the abovescheme the compound of choice for resolving into a single enantiomerwould be a compound of formula (VII). However there are no knowntechniques for the resolution of compounds of formula (VII) or similarcompounds because resolution of acids with a chiral centre so remotefrom the group used to form the diastereoisomeric derivative is unusualif not unknown. One particular difficulty associated with any processfor resolving compounds of formula (VII) is the necessity of avoidinglactonisation of the carboxylate salt to form the lactone enantiomers(VIIIa) or (VIIIb).

[0009] The applicants have devised a practical process for resolvingcompounds of formula (VII) into compounds (VIIa) and (VIIb)

[0010] wherein X is a leaving group; Y and Y¹ are independently Cl orBr; and Z is Cl, Br or a haloalkyl group without formation ofappreciable amounts of the lactones (VIII). Both compounds of formula(VIIa) and (VIIb) may be used as the starting point for making activepyrethroid insecticides. The compounds with the most desiredstereochemistry have been found to be the (−) enantiomers, which arecompounds of formula (VIIa). The stereochemistry of the compound offormula VIIa where X, Y and Y¹ are Cl and Z is CF₃ has been confirmed bythe applicants using X-ray crystallography (FIG. 1).

[0011] There is therefore provided a process for producing compounds offormula (VIIa) and (VIIb)

[0012] wherein X is a leaving group; Y and Y¹ are independently Cl orBr; and Z is Cl, Br or a haloalkyl group which process comprises:

[0013] a) reacting a compound of formula (VII)

[0014] wherein X, Y, Y¹ and Z are as defined for compounds (VIIa) and(VIIb) with a substantially optically pure chiral amine in a solvent toform a diastereoisomeric salt;

[0015] b) separating the diastereomeric salt of each enantiomer; and

[0016] c) converting the diastereomeric salt of each enantiomerseparately to compounds of formulae (VIIa) and (VIIb) by acid or basehydrolysis.

[0017] Further purification of the enantiomers may be undertaken ifnecessary or desirable.

[0018] A preferred leaving group X is Cl or Br.

[0019] Preferably Y and Y¹ are Cl.

[0020] Z is preferably Br, Cl or CF₃, especially Cl or CF₃ and mostpreferably CF₃.

[0021] The separation process of step b) may be achieved by anyconventional means, for example fractional crystallisation orchromatography. In a preferred process, separation of the diastereomericsalts is achieved by selecting chiral amines that give diastereomericsalts with different solubility characteristics. As a result, the twodiastereomeric salts can be forced into separate solvent systems, one ofthe enantiomeric salts being left in the mother liquors of the reactionmass while the other is removed.

[0022] In the context of this specification each alkyl moiety is a C₁-C₆straight or branched chain and is, for example, methyl, ethyl, n-propyl,n-butyl, n-pentyl, n-hexyl, iso-propyl, n-butyl, sec-butyl, iso-butyl,tert-butyl or neo-pentyl. Preferred alkyl groups are methyl and ethyl.

[0023] Halogen is fluorine, chlorine, bromine or iodine.

[0024] Haloalkyl groups are alkyl groups which are substituted with oneor more of the same or different halogen atoms and are, for example,CF₃, CF₂Cl, CF₃CH₂ or CHF₂CH₂ and an especially preferred group is CF₃.

[0025] Suitable amines for use in the process are R(+)-alpha methylbenzylamine and (1S,2R)-1-amino-2-indanol and the preferred amine isR(+)-alpha methyl benzylamine. The preferred molar ratio of amine toacid (VII) is 0.4-0.6, most preferably 0.5-0.55.

[0026] Suitable solvents for step a) in the process are water/methanol,aprotic solvents such as toluene and esters such as ethyl acetate orisopropyl acetate.

[0027] Preferred solvents are aprotic solvents and in particular esterssuch as isopropyl acetate.

[0028] The process of step a) is performed at between 0-80° C.,preferably at 25-65° C.

[0029] The process of step c) may be carried out using acid or base todissociate the diastereoisomeric salts, but is preferably carried outwith acid using mineral acid such as hydrochloric acid.

[0030] Isolation of the free acid can be by filtration or extractioninto a solvent which may be an haloalkane such as dichloromethane, anaprotic solvent such as toluene, an aliphatic such as hexane or an estersuch as isopropyl acetate. The process of step c) is performed at 0-50°C., preferably at 20-30° C.

[0031] If further purification of the resolved acids is required thismay be done by standard methods such as recrystallisation. Suitablesolvents include aliphatics such as hexane, isohexane or petroleumethers or aromatic solvents such as toluene. Most preferably the solventis hexane or isohexane.

[0032] The purification is performed at 0-100° C., depending upon thesolvent of choice, preferably at 20-30° C.

[0033] The applicants have also succeeded in converting the(−)-enantiomer a compound of formula (VII) to the (+) cis forms of thecompounds of the formula (III), (the stereochemistry required for makingcompounds with the highest insecticidal activity) demonstrating that thestereochemistry obtained by the process of the invention was preservedin subsequent reactions. It is already known that the (+) cis forms ofcompounds of the formula (III) are in fact the 1R cis enantiomers offormula (IIIa)

[0034] which are ultimately convertible into desirable pyrethroidproducts of formula Ia with the 1R stereochemistry

[0035] where Y and Z are as defined for formula (VII) above and E is aninsecticidally active ester moiety such as those derived from4-alkyltetrafluorobenzyl alcohols (especially 4-methyltetrafluorobenzylalcohol), 4-alkoxytetrafluorobenzyl alcohols, α-cyano-3-phenoxybenzylalcohol, 3-phenoxybenzyl alcohol and 2-methyl-3-phenylbenzyl alcohol (DArlt et al, Ang, Chem. Int. Ed. Engl. 20, 703, (1981)).

[0036] Therefore in a further aspect of the invention there is provideda process for the preparation of a single enantiomer or enantiomericallyenriched compound of formula (VI) wherein X is a leaving group such asCl or Br; Y and Y¹ are independently Cl or Br and Z is Cl, Br or ahaloalkyl group by the chlorination of a single enantiomer orenantiomerically enriched compound of formula (VII).

[0037] In yet a further aspect of the invention there is provided aprocess for the preparation of a single enantiomer or enantiomericallyenriched compound of formula (V) wherein X is a leaving group such as Clor Br; Y and Y¹ are independently Cl or Br; Z is Cl, Br or a haloalkylgroup and R is an alkyl group by the esterification of a singleenantiomer or enantiomerically enriched compound of formula (VI)

[0038] In a further aspect of the invention there is provided a processfor the preparation of a single enantiomer or enantiomerically enrichedcompound of formula (IV) wherein Y and Y¹ are independently Cl or Br; Zis Cl, Br or a haloalkyl group and R is an alkyl group by thecyclisation of a single enantiomer or enantiomerically enriched compoundof formula (V).

[0039] In yet a further aspect of the invention there is provided aprocess for the preparation of a single enantiomer or enantiomericallyenriched compound of formula (III) wherein Y is Cl or Br and Z is Cl, Bror a haloalkyl group by the hydrolysis and dehydrochlorination of asingle enantiomer or enantiomerically enriched compound of formula (IV).

[0040] In a further aspect of the invention there is provided a processfor the preparation of a single enantiomer or enantiomerically enrichedcompound of formula (II) wherein Y is Cl or Br; and Z is Cl, Br or ahaloalkyl group by the chlorination of a single enantiomer orenantiomerically enriched compound of formula (III).

[0041] In yet a further aspect of the invention there is provided aprocess for the preparation of a single enantiomer or enantiomericallyenriched compound of formula (I) wherein Y is Cl or Br and Z is Cl, Bror a haloalkyl group and E is an insecticidally active ester moiety bythe esterification of a single enantiomer or enantiomerically enrichedcompound of formula (II).

[0042] The individual steps of converting a compound of formula VII to acompound of formula I are known in the art or will be readily availableto the skilled person. Thus compounds of formula VII or theirenantiomers may be converted to compounds of formula VI or theirenantiomers by reaction with a chlorinating agent and then esterified toa compound of formula (V) as described in ‘March 4^(th) Edition—p437-38and p392’ respectively.

[0043] The (−) enantiomer of compound of formula (V) can be converted togive the required (+) enantiomer of formula (IVa), for example using theconditions given in EP-A-51355 or EP-A-3683. The other enantiomer offormula (IVb) can be prepared in a similar manner from the (+)enantiomer of (V).

[0044] 1R cis Compounds of formula (IIIa) (the + enantiomer) may beprepared by dehydrochlorinating and hydrolysing a compound of theformula (IVa) (the + enantiomer) by standard techniques, for example asdescribed in U.S. Pat. No 4,238,505, to give compound of formula (IIIa).The compound of formula (IVb) can be converted in a similar manner to acompound of formula (IIIb).

[0045] The 1R (+) enantiomer of formula (IIIa) can be converted to the1R cis acid chloride compound of formula (IIa) by standard techniques asin ‘March 4^(th) Edition—p437-38’. Similarly compounds of formula IIIbmay be converted by the same processes to compounds of formula IIb.

[0046] The 1R compounds of formula Ia may be prepared by the reaction ofa compound of formula (IIa) with an appropriate alcohol for example asgiven in EP-A-31199.

[0047] The (−) enantiomers and (+) enantiomers of compounds of formula(VII), (VI) (V) and certain compounds of formula (IV) are novel and assuch form a further aspect of the invention.

[0048] Preferably the enantiomers of compounds of formula (VII), (VI),(V) and (IV) have an enantiomeric excess greater than 90%, morepreferably greater than 98%.

[0049] The term “enantiomeric excess” is defined as:$\frac{\left( {\% \quad {major}\quad {enantiomer}} \right) - \left( {\% \quad {minor}\quad {enantiomer}} \right)}{\left( {\% \quad {major}\quad {enantiomer}} \right) + \left( {\% \quad {minor}\quad {enantiomer}} \right)}$

[0050] Certain compounds of formula (I) are also novel and form yetanother aspect of the invention.

[0051] The compounds of formula (I) can be used to combat and controlinfestations of insect pests such as Lepidoptera, Diptera, Hemiptera,Thysanoptera, Orthoptera, Dictyoptera, Coleoptera, Siphonaptera,Hymenoptera and Isoptera and also other invertebrate pests, for example,acarine, nematode and mollusc pests. Insects, acarines, nematodes andmolluscs are hereinafter collectively referred to as pests. The pestswhich may be combated and controlled by the use of the inventioncompounds include those pests associated with agriculture (which termincludes the growing of crops for food and fibre products), horticultureand animal husbandry, companion animals, forestry and the storage ofproducts of vegetable origin (such as fruit, grain and timber); thosepests associated with the damage of man-made structures and thetransmission of diseases of man and animals; and also nuisance pests(such as flies).

[0052] Examples of pest species which may be controlled by the compoundsof formula (I) include: Myzus persicae (aphid), Aphis gossypii (aphid),Aphis fabae (aphid), Lygus spp. (capsids), Dysdercus spp. (capsids),Nilaparvata lugens (planthopper), Nephotettixc incticeps (leafhopper),Nezara spp. (stinkbugs), Euschistus spp. (stinkbugs), Leptocorisa spp.(stinkbugs), Frankliniella occidentalis (thrip), Thrips spp. (thrips),Leptinotarsa decemlineata (Colorado potato beetle), Anthonomus grandis(boll weevil), Aonidiella spp. (scale insects), Trialeurodes spp. (whiteflies), Bemisia tabaci (white fly), Ostrinia nubilalis (European cornborer), Spodoptera littoralis (cotton leafworm), Heliothis virescens(tobacco budworm), Helicoverpa armigera (cotton bollworm), Helicoverpazea (cotton bollworm), Sylepta derogata (cotton leaf roller), Pierisbrassicae (white butterfly), Plutella xylostella (diamond back moth),Agrotis spp. (cutworms), Chilo suppressalis (rice stem borer), Locustamigratoria (locust), Chortiocetes terminifera (locust), Diabrotica spp.(rootworms), Panonychus ulmi (European red mite), Panonychus citri(citrus red mite), Tetranychus urticae (two-spotted spider mite),Tetranychus cinnabarinus (carmine spider mite), Phyllocoptruta oleivora(citrus rust mite), Polyphagotarsonemus latus (broad mite), Brevipalpusspp. (flat mites), Boophilus microplus (cattle tick), Dermacentorvariabilis (American dog tick), Ctenocephalides felis (cat flea),Liriomyza spp. (leafminer), Musca domestica (housefly), Aedes aegypti(mosquito), Anopheles spp. (mosquitoes), Culex spp. (mosquitoes),Lucillia spp. (blowflies), Blattella germanica (cockroach), Periplanetaamericana (cockroach), Blatta orientalis (cockroach), termites of theMastotermitidae (for example Mastotermes spp.), the Kalotemitidae (forexample Neotermes spp.), the Rhinotermitidae (for example Coptotermesformosanus, Reticulitermes flavipes, R. speratu, R. virginicus, R.hesperus, and R. santonensis) and the Termitidae (for exampleGlobitermes sulphureus), Solenopsis geminata (fire ant), Monomoriumpharaonis (pharaoh's ant), Damalinia spp. and Linognathus spp. (bitingand suckling lice), Meloidogyne spp. (root knot nematodes), Globoderaspp. and Heterodera spp. (cyst nematodes), Pratylenchus spp. (lesionnematodes), Rhodopholus spp. (banana burrowing nematodes), Tylenchulusspp.(citrus nematodes), Haemonchus contortus (barber pole worm),Caenorhabditis elegans (vinegar eelworm), Trichostrongylus spp. (gastrointestinal nematodes) and Deroceras reticulatum (slug).

[0053] The invention therefore provides a method of combating andcontrolling insects, acarines, nematodes or molluscs which comprisesapplying an insecticidally, acaricidally, nematicidally ormolluscicidally effective amount of a novel compound of formula (I), ora composition containing a novel compound of formula (I), to a pest, alocus of pest, or to a plant susceptible to attack by a pest. Thecompounds of formula (I) are preferably used against insects, acarinesor nematodes.

[0054] In order to apply a compound of formula (I) to a pest, a locus ofpest, or to a plant susceptible to attack by a pest, a compound offormula (I) is usually formulated into a composition which includes, inaddition to the compound of formula (I), a suitable inert diluent orcarrier and, optionally, a surface active agent (SFA). SFAs arechemicals which are able to modify the properties of an interface (forexample, liquid/solid, liquid/air or liquid/liquid interfaces) bylowering the interfacial tension and thereby leading to changes in otherproperties (for example dispersion, emulsification and wetting). It ispreferred that all compositions (both solid and liquid formulations)comprise, by weight, 0.0001 to 95%, more preferably 1 to 85%, forexample 5 to 60%, of a compound of formula (I). The composition isgenerally used for the control of pests such that a compound of formula(I) is applied at a rate of from 0.1 g to 10 kg per hectare, preferablyfrom 1 g to 6 kg per hectare, more preferably from 1 g to 1 kg perhectare.

[0055] When used in a seed dressing, a compound of formula (I) is usedat a rate of 0.0001 g to 10 g (for example 0.001 g or 0.05 g),preferably 0.005 g to 10 g, more preferably 0.005 g to 4 g, per kilogramof seed.

[0056] In another aspect the present invention provides an insecticidal,acaricidal, nematicidal or molluscicidal composition comprising aninsecticidally, acaricidally, nematicidally or molluscicidally effectiveamount of a novel compound of formula (I) and a suitable carrier ordiluent therefor. The composition is preferably an insecticidal,acaricidal or nematicidal composition.

[0057] In a still further aspect the invention provides a method ofcombating and controlling pests at a locus which comprises treating thepests or the locus of the pests with an insecticidally, acaricidally,nematicidally or molluscicidally effective amount of a compositioncomprising a novel compound of formula (I). The compounds of formula (I)are preferably used against insects, acarines or nematodes.

[0058] The compositions can be chosen from a number of formulationtypes, including dustable powders (DP), soluble powders (SP), watersoluble granules (SG), water dispersible granules (WG), wettable powders(WP), granules (GR) (slow or fast release), soluble concentrates (SL),oil miscible liquids (OL), ultra low volume liquids (UL), emulsifiableconcentrates (EC), dispersible concentrates (DC), emulsions (both oil inwater (EW) and water in oil (EO)), micro-emulsions (ME), suspensionconcentrates (SC), aerosols, fogging/smoke formulations, capsulesuspensions (CS) and seed treatment formulations. The formulation typechosen in any instance will depend upon the particular purpose envisagedand the physical, chemical and biological properties of the compound offormula

[0059] Dustable powders (DP) may be prepared by mixing a compound offormula (I) with one or more solid diluents (for example natural clays,kaolin, pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr,chalk, diatomaceous earths, calcium phosphates, calcium and magnesiumcarbonates, sulphur, lime, flours, talc and other organic and inorganicsolid carriers) and mechanically grinding the mixture to a fine powder.

[0060] Soluble powders (SP) may be prepared by mixing a compound offormula (I) with one or more water-soluble inorganic salts (such assodium bicarbonate, sodium carbonate or magnesium sulphate) or one ormore water-soluble organic solids (such as a polysaccharide) and,optionally, one or more wetting agents, one or more dispersing agents ora mixture of said agents to improve water dispersibility/solubility. Themixture is then ground to a fine powder. Similar compositions may alsobe granulated to form water soluble granules (SG).

[0061] Wettable powders (WP) may be prepared by mixing a compound offormula (I) with one or more solid diluents or carriers, one or morewetting agents and, preferably, one or more dispersing agents and,optionally, one or more suspending agents to facilitate the dispersionin liquids. The mixture is then ground to a fine powder. Similarcompositions may also be granulated to form water dispersible granules(WG).

[0062] Granules (GR) may be formed either by granulating a mixture of acompound of formula (I) and one or more powdered solid diluents orcarriers, or from pre-formed blank granules by absorbing a compound offormula (I) (or a solution thereof, in a suitable agent) in a porousgranular material (such as pumice, attapulgite clays, fuller's earth,kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing acompound of formula (I) (or a solution thereof, in a suitable agent) onto a hard core material (such as sands, silicates, mineral carbonates,sulphates or phosphates) and drying if necessary. Agents which arecommonly used to aid absorption or adsorption include solvents (such asaliphatic and aromatic petroleum solvents, alcohols, ethers, ketones andesters) and sticking agents (such as polyvinyl acetates, polyvinylalcohols, dextrins, sugars and vegetable oils). One or more otheradditives may also be included in granules (for example an emulsifyingagent, wetting agent or dispersing agent).

[0063] Dispersible Concentrates (DC) may be prepared by dissolving acompound of formula (I) in water or an organic solvent, such as aketone, alcohol or glycol ether. These solutions may contain a surfaceactive agent (for example to improve water dilution or preventcrystallisation in a spray tank).

[0064] Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) maybe prepared by dissolving a compound of formula (I) in an organicsolvent (optionally containing one or more wetting agents, one or moreemulsifying agents or a mixture of said agents). Suitable organicsolvents for use in ECs include aromatic hydrocarbons (such asalkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100,SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark),ketones (such as cyclohexanone or methylcyclohexanone) and alcohols(such as benzyl alcohol, furfuryl alcohol or butanol),N-alkylpyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone),dimethyl amides of fatty acids (such as C₈-C₁₀ fatty acid dimethylamide)and chlorinated hydrocarbons. An EC product may spontaneously emulsifyon addition to water, to produce an emulsion with sufficient stabilityto allow spray application through appropriate equipment. Preparation ofan EW involves obtaining a compound of formula (I) either as a liquid(if it is not a liquid at room temperature, it may be melted at areasonable temperature, typically below 70° C.) or in solution (bydissolving it in an appropriate solvent) and then emulsiflying theresultant liquid or solution into water containing one or more SFAs,under high shear, to produce an emulsion. Suitable solvents for use inEWs include vegetable oils, chlorinated hydrocarbons (such aschlorobenzenes), aromatic solvents (such as alkylbenzenes oralkylnaphthalenes) and other appropriate organic solvents which have alow solubility in water.

[0065] Microemulsions (ME) may be prepared by mixing water with a blendof one or more solvents with one or more SFAs, to produce spontaneouslya thermodynamically stable isotropic liquid formulation. A compound offormula (I) is present initially in either the water or the solvent/SFAblend. Suitable solvents for use in MEs include those hereinbeforedescribed for use in in ECs or in EWs. An ME may be either anoil-in-water or a water-in-oil system (which system is present may bedetermined by conductivity measurements) and may be suitable for mixingwater-soluble and oil-soluble pesticides in the same formulation. An MEis suitable for dilution into water, either remaining as a microemulsionor forming a conventional oil-in-water emulsion.

[0066] Suspension concentrates (SC) may comprise aqueous or non-aqueoussuspensions of finely divided insoluble solid particles of a compound offormula (I). SCs may be prepared by ball or bead milling the solidcompound of formula (I) in a suitable medium, optionally with one ormore dispersing agents, to produce a fine particle suspension of thecompound. One or more wetting agents may be included in the compositionand a suspending agent may be included to reduce the rate at which theparticles settle. Alternatively, a compound of formula (I) may be drymilled and added to water, containing agents hereinbefore described, toproduce the desired end product.

[0067] Aerosol formulations comprise a compound of formula (I) and asuitable propellant (for example n-butane). A compound of formula (I)may also be dissolved or dispersed in a suitable medium (for examplewater or a water miscible liquid, such as n-propanol) to providecompositions for use in non-pressurised, hand-actuated spray pumps.

[0068] A compound of formula (I) may be mixed in the dry state with apyrotechnic mixture to form a composition suitable for generating, in anenclosed space, a smoke containing the compound.

[0069] Capsule suspensions (CS) may be prepared in a manner similar tothe preparation of EW formulations but with an additional polymerisationstage such that an aqueous dispersion of oil droplets is obtained, inwhich each oil droplet is encapsulated by a polymeric shell and containsa compound of formula (I) and, optionally, a carrier or diluenttherefor. The polymeric shell may be produced by either an interfacialpolycondensation reaction or by a coacervation procedure. Thecompositions may provide for controlled release of the compound offormula (I) and they may be used for seed treatment. A compound offormula (I) may also be formulated in a biodegradable polymeric matrixto provide a slow, controlled release of the compound.

[0070] A composition may include one or more additives to improve thebiological performance of the composition (for example by improvingwetting, retention or distribution on surfaces; resistance to rain ontreated surfaces; or uptake or mobility of a compound of formula (I)).Such additives include surface active agents, spray additives based onoils, for example certain mineral oils or natural plant oils (such assoy bean and rape seed oil), and blends of these with otherbio-enhancing adjuvants (ingredients which may aid or modify the actionof a compound of formula (I)).

[0071] A compound of formula (I) may also be formulated for use as aseed treatment, for example as a powder composition, including a powderfor dry seed treatment (DS), a water soluble powder (SS) or a waterdispersible powder for slurry treatment (WS), or as a liquidcomposition, including a flowable concentrate (FS), a solution (LS) or acapsule suspension (CS). The preparations of DS, SS, WS, FS and LScompositions are very similar to those of, respectively, DP, SP, WP, SCand DC compositions described above. Compositions for treating seed mayinclude an agent for assisting the adhesion of the composition to theseed (for example a mineral oil or a film-forming barrier).

[0072] Wetting agents, dispersing agents and emulsifying agents may besurface SFAs of the cationic, anionic, amphoteric or non-ionic type.

[0073] Suitable SFAs of the cationic type include quaternary ammoniumcompounds (for example cetyltrimethyl ammonium bromide), imidazolinesand amine salts.

[0074] Suitable anionic SFAs include alkali metals salts of fatty acids,salts of aliphatic monoesters of sulphuric acid (for example sodiumlauryl sulphate), salts of sulphonated aromatic compounds (for examplesodium dodecylbenzenesulphonate, calcium dodecylbenzenesulphonate,butylnaphthalene sulphonate and mixtures of sodium di-isopropyl- andtri-isopropyl-naphthalene sulphonates), ether sulphates, alcohol ethersulphates (for example sodium laureth-3-sulphate), ether carboxylates(for example sodium laureth-3-carboxylate), phosphate esters (productsfrom the reaction between one or more fatty alcohols and phosphoric acid(predominately mono-esters) or phosphorus pentoxide (predominatelydi-esters), for example the reaction between lauryl alcohol andtetraphosphoric acid; additionally these products may be ethoxylated),sulphosuccinamates, paraffin or olefine sulphonates, taurates andlignosulphonates.

[0075] Suitable SFAs of the amphoteric type include betaines,propionates and glycinates.

[0076] Suitable SFAs of the non-ionic type include condensation productsof alkylene oxides, such as ethylene oxide, propylene oxide, butyleneoxide or mixtures thereof, with fatty alcohols (such as oleyl alcohol orcetyl alcohol) or with alkylphenols (such as octylphenol, nonylphenol oroctylcresol); partial esters derived from long chain fatty acids orhexitol anhydrides; condensation products of said partial esters withethylene oxide; block polymers (comprising ethylene oxide and propyleneoxide); alkanolamides; simple esters (for example fatty acidpolyethylene glycol esters); amine oxides (for example lauryl dimethylamine oxide); and lecithins.

[0077] Suitable suspending agents include hydrophilic colloids (such aspolysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose)and swelling clays (such as bentonite or attapulgite).

[0078] A compound of formula (I) may be applied by any of the knownmeans of applying pesticidal compounds. For example, it may be applied,formulated or unformulated, to the pests or to a locus of the pests(such as a habitat of the pests, or a growing plant liable toinfestation by the pests) or to any part of the plant, including thefoliage, stems, branches or roots, to the seed before it is planted orto other media in which plants are growing or are to be planted (such assoil surrounding the roots, the soil generally, paddy water orhydroponic culture systems), directly or it may be sprayed on, dustedon, applied by dipping, applied as a cream or paste formulation, appliedas a vapour or applied through distribution or incorporation of acomposition (such as a granular composition or a composition packed in awater-soluble bag) in soil or an aqueous environment.

[0079] A compound of formula (I) may also be injected into plants orsprayed onto vegetation using electrodynamic spraying techniques orother low volume methods, or applied by land or aerial irrigationsystems.

[0080] Compositions for use as aqueous preparations (aqueous solutionsor dispersions) are generally supplied in the form of a concentratecontaining a high proportion of the active ingredient, the concentratebeing added to water before use. These concentrates, which may includeDCs, SCs, ECs, EWs, MEs SGs, SPs, WPs, WGs and CSs, are often requiredto withstand storage for prolonged periods and, after such storage, tobe capable of addition to water to form aqueous preparations whichremain homogeneous for a sufficient time to enable them to be applied byconventional spray equipment. Such aqueous preparations may containvarying amounts of a compound of formula (I) (for example 0.0001 to 10%,by weight) depending upon the purpose for which they are to be used.

[0081] A compound of formula (I) may be used in mixtures withfertilisers (for example nitrogen-, potassium- or phosphorus-containingfertilisers). Suitable formulation types include granules of fertiliser.The mixtures suitably contain up to 25% by weight of the compound offormula (I).

[0082] The invention therefore also provides a fertiliser compositioncomprising a fertiliser and a novel compound of formula (I).

[0083] The compound of formula (I) may be the sole active ingredient ofthe composition or it may be admixed with one or more additional activeingredients such as a pesticide, fungicide, synergist, herbicide orplant growth regulator where appropriate. An additional activeingredient may: provide a composition having a broader spectrum ofactivity or increased persistence at a locus; synergise the activity orcomplement the activity (for example by increasing the speed of effector overcoming repellency) of the compound of formula (I); or help toovercome or prevent the development of resistance to individualcomponents. The particular additional active ingredient will depend uponthe intended utility of the composition.

[0084] Examples of suitable pesticides include the following:

[0085] a) Pyrethroids, such as permethrin, cypermethrin, fenvalerate,esfenvalerate, deltamethrin, cyhalothrin (in particularlambda-cyhalothrin), bifenthrin, fenpropathrin, cyfluthrin, tefluthrin,fish safe pyrethroids (for example ethofenprox), natural pyrethrin,tetramethrin, s-bioallethrin, fenfluthrin, prallethrin or5-benzyl-3-furylmethyl-(E,-(1R,3S)-2,2-dimethyl-3-(2-oxothiolan-3-ylidenemethyl)cyclopropanecarboxylate;

[0086] b) Organophosphates, such as, profenofos, sulprofos, acephate,methyl parathion, azinphos-methyl, demeton-s-methyl, heptenophos,thiometon, fenamiphos, monocrotophos, profenofos, triazophos,methamidophos, dimethoate, phosphamidon, malathion, chlorpyrifos,phosalone, terbufos, fensulfothion, fonofos, phorate, phoxim,pirimiphos-methyl, pirimiphos-ethyl, fenitrothion, fosthiazate ordiazinon;

[0087] c) Carbamates (including aryl carbamates), such as pirimicarb,triazamate, cloethocarb, carbofuran, furathiocarb, ethiofencarb,aldicarb, thiofurox, carbosulfan, bendiocarb, fenobucarb, propoxur,methomyl or oxamyl;

[0088] d) Benzoyl ureas, such as diflubenzuron, triflumuron,hexaflumuron, flufenoxuron or chlorfluazuron;

[0089] e) Organic tin compounds, such as cyhexatin, fenbutatin oxide orazocyclotin;

[0090] f) Pyrazoles, such as tebufenpyrad and fenpyroximate;

[0091] g) Macrolides, such as avermectins or milbemycins, for exampleabamectin, emamectin benzoate, ivermectin, milbemycin, spinosad orazadirachtin;

[0092] h) Hormones or pheromones;

[0093] i) Organochlorine compounds such as endosulfan, benzenehexachloride, DDT, chlordane or dieldrin;

[0094] j) Amidines, such as chlordimeform or amitraz;

[0095] k) Fumigant agents, such as chloropicrin, dichloropropane, methylbromide or metam;

[0096] l) Chloronicotinyl compounds such as imidacloprid, thiacloprid,acetamiprid, nitenpyram or thiamethoxam;

[0097] m) Diacylhydrazines, such as tebufenozide, chromafenozide ormethoxyfenozide;

[0098] n) Diphenyl ethers, such as diofenolan or pyriproxifen;

[0099] o) Indoxacarb;

[0100] p) Chlorfenapyr; or

[0101] q) Pymetrozine.

[0102] In addition to the major chemical classes of pesticide listedabove, other pesticides having particular targets may be employed in thecomposition, if appropriate for the intended utility of the composition.For instance, selective insecticides for particular crops, for examplestemborer specific insecticides (such as cartap) or hopper specificinsecticides (such as buprofezin) for use in rice may be employed.Alternatively insecticides or acaricides specific for particular insectspecies/stages may also be included in the compositions (for exampleacaricidal ovo-larvicides, such as clofentezine, flubenzimine,hexythiazox or tetradifon; acaricidal motilicides, such as dicofol orpropargite; acaricides, such as bromopropylate or chlorobenzilate; orgrowth regulators, such as hydramethylnon, cyromazine, methoprene,chlorfluazuron or diflubenzuron).

[0103] Examples of suitable synergists for use in the compositionsinclude piperonyl butoxide, sesamex, safroxan and dodecyl imidazole.

[0104] Suitable herbicides and plant-growth regulators for inclusion inthe compositions will depend upon the intended target and the effectrequired.

[0105] An example of a rice selective herbicide which may be included ispropanil. An example of a plant growth regulator for use in cotton isPIX™.

[0106] Some mixtures may comprise active ingredients which havesignificantly different physical, chemical or biological properties suchthat they do not easily lend themselves to the same conventionalformulation type. In these circumstances other formulation types may beprepared. For example, where one active ingredient is a water insolublesolid and the other a water insoluble liquid, it may nevertheless bepossible to disperse each active ingredient in the same continuousaqueous phase by dispersing the solid active ingredient as a suspension(using a preparation analogous to that of an SC) but dispersing theliquid active ingredient as an emulsion (using a preparation analogousto that of an EW). The resultant composition is a suspoemulsion (SE)formulation.

[0107] The following examples illustrate the processes and the compoundsof this invention.

[0108] Chiral GLC Method for Analysis of Enantiomers

[0109] The following GLC method was used to analyse compounds of theformula (VII)

[0110] Column Chiraldex CB 25 m, 0.25 mm, 25 micron

[0111] Carrier gas helium

[0112] 80° C. start temp. for 5 minutes, 2° C./min ramp rate to 120° C.,10° C./min ramp rate to 160° C.,

[0113] final time 2 minutes, total time 31 mins

[0114] Injector temp 250° C.

[0115] Detector temp 250° C.

[0116] It was established that the enantiomer of (VII) (Y,Y¹ and X═Cl,Z═CF₃) with a (−) rotation eluted at 20.5 min. and that with a (+)rotation eluted at 21.3 min.

EXAMPLE 1 Preparation of the (−) Enantiomer of4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid

[0117] Step A

[0118] Isopropyl acetate (400 ml) and4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid (54 gm) werecharged to a clean, dry 1 litre jacketed reaction flask fitted withturbine agitator. The contents of the reactor were agitated at roomtemperature and R-(+)-α-methyl benzylamine (12.4 gm) was added slowlyover 30 minutes producing a small exotherm. The reactor contents werethen stirred for 2 days at room temperature after which time a finewhite dispersion was obtained. The salt was filtered off on a sinterednutche and washed with a minimal ethyl acetate (˜20 ml) followed byhexane (50 ml) and the white product pulled ‘dry’ on the nutche. Yield17.7. gm.

[0119] Step B

[0120] The diastereomeric salt produced in step A was discharged into a250 ml conical flask together with dichloromethane (50 ml). The flaskcontents were stirred on a magnetic stirrer whilst 2 molar hydrochloricacid was charged (50 ml) and stirred to dissolve up the solids. Theflask contents were then separated in a separating flask and the organiclayer washed with further (50 ml) 2 molar hydrochloric acid, followed bya water wash (50 ml) and a brine wash (25 ml). The organic layer wasthen topped to give a crystalline white solid (12.5 gm, 46%). Chiral GCanalysis of the product revealed it to be 85% e.e. The crude product wasrecrystallised by dissolving in hexane (175 ml) and heating to 50° C.with agitation. The resultant colourless solution was then cooled in thefridge (+4° C.) to produce a small amount of white crystalline solidwhich was filtered off (2.52 gm) and found to be a mixture of the twoenantiomers, 60% e.e. by chiral GC. The hexane filtrates were distilledto produce a white crystalline solid (9.2 gm), which was analysed bychiral GC as 92% e.e. of the required (−) enantiomer of4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid. Polarimetryon the enantiomer obtained in dichloromethane (12.34 g/litre) gave an∝_(D)=−24° The stereochemistry of the compound was confirmed by X-raycrystallography under the conditions set out in Table 1. Atomiccoordinates are set out in Table 2 and the X-ray crystal structure inshown in FIG. I. TABLE 1 Empirical formula C9 H12 C13 F3 O2 Formulaweight 315.54 Temperature 293(2) K Wavelength 0.71073 Å Crystal systemTriclinic Space group P1 Unit cell dimensions a = 6.4022(13) Å α =98.57(3)°. b = 8.8160(18) Å β = 95.87(3)°. c = 12.393(3) Å γ =105.41(3)°. Volume 659.4(2) Å³ Z 2 Density (calculated) 1.589 Mg/m³Absorption coefficient 0.717 mm⁻¹ F(000) 320 Crystal size 0.2 × 0.1 ×0.08 mm³ Theta range for data collection 1.68 to 24.99°. Index ranges −5<= h <= 7, −10 <= k <= 10, −14 <= 1 <= 14 Reflections collected 2968Independent reflections 2968 [R(int) = 0.0000] Completeness to theta =24.99° 95.0% Absorption correction Scalepack Refinement methodFull-matrix least-squares on F² Data/restraints/parameters 2968/15/312Goodness-of-fit on F² 1.042 Final R indices [I > 2sigma(I)] R1 = 0.1114,wR2 = 0.2830 R indices (all data) R1 = 0.1668, wR2 = 0.3 179 Absolutestructure parameter 0.0(3) Extinction coefficient 0.057(15) Largestduff, peak and hole 0.892 and −0.534 e.Å⁻³

[0121] TABLE 2 Atomic coordinates (×10⁴) and equivalent isotropicdisplacement parameters (Å² × 10³). U(eq) is defined as one third of thetrace of the orthogonalized U^(ij) tensor. x y z U(eq) C(4A) 710(40)−5490(30) −4096(19) 55(6) C(5B) −4400(40) 830(30) 1912(18) 54(6) C(5A)−820(30) −5800(20) −2343(17) 50(6) C(8B) −1800(30) 5640(30) 1390(20)62(7) C(7B) −3580(30) 4210(20) 1560(17) 44(5) C(3A) −1090(30) −5300(20)−3452(17) 39(5) F(3A) −4090(30) −11180(20) −4085(14) 97(5) C(2B)−6910(30) −160(30) 50(20) 58(7) C(8A) −5810(30) −9270(30) −4515(18)46(5) C(1B) −5500(30) −770(20) −552(15) 32(4) C(4B) −7890(40) 1670(30)1540(20) 62(7) C(1A) −2270(40) −2810(20) −2502(16) 42(5) C(9A) −5550(40)−10950(30) −4850(20) 62(7) C(2A) −870(30) −35 10(30) −3222(15) 39(5)C(6A) −3440(40) −6280(20) −4110(18) 52(6) C(6B) −4560(40) 2750(30)652(18) 58(6) O(1A) −4000(20) −3571(18) −2346(11) 52(4) F(1B) 320(20)5712(18) 3074(10) 85(5) O(2A) −1230(20) −1285(18) −2002(11) 54(4) O(1B)−6510(20) −2279(17) −1110(11) 54(4) O(2B) −3600(20) −120(16) −634(11)51(4) F(3B) 1020(20) 7841(15) 2372(9)  65(4) F(1A) −7460(20) −12116(15)−4925(11) 68(4) F(2B) −1860(30) 7152(18) 3102(13) 87(5) F(2A) −4830(20)−11113(15) −5805(11) 58(3) Cl(3B) −2742(10) 6989(7)  676(6)  76(2)Cl(2A) −6736(10) −9110(7)  −3215(5)  68(2) Cl(1B) −6141(9)  3334(7) −490(5)  57(2) Cl(1A) −4111(9)  −5437(7)  −5300(4)  54(2) Cl(3A)−7779(8)  −9032(7)  −5528(5)  58(2) Cl(2B) 131(8)  4973(7)  660(5) 57(2) C(9B) −600(40) 6560(30) 2440(20) 57(6) C(3B) −6000(30) 1320(20)1007(15) 38(5) C(7A) −3530(30) −7980(20) −4433(19) 48(5)

EXAMPLE 2 Recovery of R-(+)-α-methyl benzylamine

[0122] The isopropyl acetate mother liquor and ethyl acetate washes,from the chiral diastereomeric salt formation of Example 1, werecombined and washed with 2 molar hydrochloric acid (2×50 ml), water (50ml) and brine (25 ml). All separated well and were combined. Theresultant aqueous liquor was washed with DCM (50 ml) then adjusted topH>9 with 47% sodium hydroxide solution before extracting with DCM (100ml). Topping off the resultant organic layer yielded a brown oil whichrepresented a 95% recovery of R-(+)-α-methyl benzylamine.

EXAMPLE 3 Preparation of the (+) Enantiomer of4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid

[0123] The combined isopropyl acetate mother liquor/ethyl acetate washesfrom Example 1, after acid washing, was topped to yield a straw colouredsolid (41.7 gm), which proved, by chiral GC, to be 32% e.e. compound ofthe (+) enantiomer of4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid.

EXAMPLE 4 Preparation of the (−) Enantiomer of4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid

[0124] Step A

[0125] 4,6,6-Trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid (45.1gm-0.143 moles) was dissolved in water (120 ml) and methanol (180 ml) in1 litre jacketed reaction flask fitted with turbine agitator, condenser,nitrogen purge and thermometer. The reactor contents were agitatedwhilst sodium carbonate (10.38 gm-0.074 moles) was added to dissolve theacid and the pH adjusted to 7.4. The reactor contents were heated to 50°C. to ensure complete solution. R(+)-alpha methyl benzylamine (9.11gm-0.074 moles) was agitated in a 500 ml conical flask fitted withmagnetic stirrer together with water (250 ml). Hydrochloric acid (38 ml2 molar) was then slowly added to dissolve up the amine giving a finalpH of 2.5. The pH of the solution was adjusted with a few drops of 47%sodium hydroxide solution to pH 6. A dropping funnel was fitted to theacid solution reactor and the amine solution charged to it. The aminesolution was then run into the acid solution at 50° C. over a period of2 hours. When the addition was complete the reaction mass was heated fora further 30 minutes before allowing the contents to self cool—thereactor contents were allowed to cool overnight with agitation andprecipitated a white solid. The final slurry was filtered off on asintered nutche and pulled dry. The paste was given a small watermethanol wash (20 ml water plus 40 ml methanol) and pulled dry. Yield39.3 gm. The paste was slurried with 2 molar hydrochloric acid anddichloromethane (200 ml of each) and agitated to dissolve. The twophases were separated and the organic layer treated with a second acidwash (200 ml) in the same way before applying a water (200 ml) and brine(100 ml) wash. The organic layer was then separated and the solventremoved on a rotary evaporator at 50° C. to give a pale yellow oil whichsolidified on cooling. Yield 28.8 gm.

[0126] Step B

[0127] The solidified product from step A was dissolved in hexane (190ml) with agitation at 50° C. and then cooled to cool to 4° C. over 3hours. A heavy white crystalline solid was formed which was filtered off(12.8 gm) and pulled ‘dry’. Chiral GLC revealed this crystallinematerial was close to a racemic mixture of4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid. Theresultant hexane filtrates were then evaporated on a rotary evaporatorat 50° C. to give a yellow oil which solidified to a waxy yellow solid(5.9 gm). This solid was purified by column chromatography in twocolumns—each 2.9 gm of crude enantiomer onto an 80 gm silica column with3 litres of 50:50 dichloromethane:hexane eluent. The combined productfrom the columns yielded a crystalline product (3.2 gm, 14% yield). DSCanalysis of the enantiomer gave a melting point of 61° C. and a molarpurity of 92.8%. Chiral GC showed the material to be 90% e.e. of therequired (−) enantiomer of4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid.

EXAMPLE 5 Preparation of the (+) Enantiomer of4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid

[0128] Step A

[0129] Toluene (500 ml) and4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid (80.1 gm)were charged to a clean/dry 1 litre jacketed reaction flask fitted withturbine agitator. The contents of the reactor were agitated at roomtemperature in an attempt to dissolve the acid but some acid stillremained. (1R,2S)-1-Amino-2-indanol (16.2 gm) was charged and themixture stirred further at room temperature slowly dissolving to form apale yellow solution. The reactor contents were stirred overnightproducing a thick slurry which was filtered off and washed with a littletoluene followed by hexane and eventually pulled ‘dry’ on the nutche.Yield 30.9 gm.

[0130] Step B

[0131] The diastereomeric salt was slurried in dichloromethane (100 ml)and given 2 molar hydrochloric acid washes (3×50 ml) and a brine wash(50 ml). The organic phase was then topped to yield a very paleyellow/off white crystalline solid (21.4 gm). Chiral GC showed theproduct to be 40% e.e. of the (+) enantiomer of4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid.

[0132] Step C

[0133] The isolated solid was dissolved in hexane (150 ml) at 50° C. andwas then cooled to 4° C. for 4 hours yielding a white crystalline solid,which was filtered off (11.5 gm). The hexane mother liquor was thentopped to yield a pale yellow oil which solidified on standing (8.8 gm).Chiral GC showed this solid to be 66% e.e.. of the (+) enantiomer4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid. Furthercrystallisation was carried out on the solid using hexane (50 ml)producing a white crystalline solid (4.6 gm). The resultant hexanemother liquor was then topped to give a pale yellow solid (4.3 gm).Chiral GC on these products showed them to be to be 60% e.e. and 74%e.e. respectively of the (+) enantiomer of4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid. The latterof the two was re-dissolved in hexane (50 ml) and treated in the sameway to give a third crystalline solid (1.1 gm), and material from thetopped hexane mother liquor (2.9 gm, 7% yield as SE). Chiral GC showedthem to be to be 56% e.e. and 90% e.e. respectively of the (+)enantiomer. Polarimetry of the 90% e.e. product in dichioromethane at20° C. (12.07 gm/litre) gave an ∝_(D)=+28°

EXAMPLE 6 Preparation of the (−) methyl ester of4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid

[0134] Step A

[0135] 4,6,6-Trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid (−)enantiomer (20.0-0.063 moles, of 80% e.e. as judged by chiral GLC) wascharged to a clean, dry 100 ml 3 necked flask fitted with thermometer,condenser, nitrogen purge and magnetic stirrer. Toluene (65 ml) andtriethylamine (2 drops) were charged and the reactor contents agitatedwhilst heating to 70° C. with an external oil bath. Thionyl chloride(9.12 ml, 14.9 gm-0.125 moles) was added to the reaction flask bysyringe over 45 minutes. The reactor contents were then allowed to cooland stirred overnight.

[0136] The following day the reactor contents were topped on a rotaryevaporator and dichloromethane (30 ml) charged. This was also topped onthe rotary evaporator to remove residual thionyl chloride, sulphurdioxide and hydrogen chloride from the acid chloride reaction. Ayellow/brown oil was obtained (21.3 gm) which was analysed by GLC, GCMSand NMR to confirm the material was the acid chloride of4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid.

[0137] Polarimetry of the acid chloride (6.24 gm/litre at 20° C.) indichloromethane gave an ∝_(D)=−24.0°.

[0138] Step B

[0139] The acid chloride obtained in step A (20.0 gm-0.063 mol) was runinto dry methanol (30 ml) which was stirred in a clean dry 100 mlreaction flask fitted with thermometer, condenser, nitrogen purge andmagnetic stirrer. The reactor contents were stirred for a further 50hours before topping off the methanol on a rotary evaporator to yield ared/brown oil (19.13 gm) which was analysed by GLC, GCMS and NMR toconfirm the material was the methyl ester of4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid. Polarimetryof the methyl ester in dichloromethane (12.25 gm/litre at 20° C.) gavean ∝_(D)=−23°.

EXAMPLE 7 Preparation of the (−) methyl ester of4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid

[0140] 4,6,6-Trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid (−)enantiomer (1.39 gm-0.004 moles, of 90% e.e. as judged by chiral GLC)was charged to a clean, dry 25 ml 3 necked flask fitted withthermometer, condenser, nitrogen purge and magnetic stirrer. Toluene (5ml) and triethylamine (2 drops) were charged and the reactor contentsagitated whilst heating to 70° C. with an external oil bath. Thionylchloride (1.04 gm-0.009 moles) was added to the reaction flask bysyringe over 20 minutes. The reactor contents were then allowed to cooland stirred overnight. The following day the reactor contents weretopped on a rotary evaporator and toluene (5 ml) charged. This was alsotopped on the rotary evaporator to remove residual thionyl chloride,sulphur dioxide and hydrogen chloride from the acid chloride reaction. Ayellow/brown oil was obtained which immediately quenched into drymethanol (10 ml) with agitation in a clean dry 25 ml flask agitated by amagnetic stirrer for 15 hours. Analysis by GLC showed the reaction to becomplete and the solvent was topped to leave a pale yellow oil. The oilwas dissolved in dichloromethane and washed with 2 molar hydrochloricacid twice, water then brine. After drying the product was topped toyield a pale yellow oil (0.99 gm).

EXAMPLE 8 Preparation of the (+) methyl ester of4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid

[0141] Step A

[0142] 4,6,6-Trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid (+)enantiomer (9.13 gm-0.029 moles, of 80% e.e. as judged by chiral GLC)was charged to a clean dry 100 ml 3 necked flask fitted withthermometer, condenser, nitrogen purge and magnetic stirrer. Toluene (32ml) and triethylamine (2 drops) were charged and the reactor contentsagitated whilst heating to 70° C. with an external oil bath. Thionylchloride (4.16 ml, 6.78 gm-0.057 moles) was added to the reaction flaskby syringe over 45 minutes. The reactor contents were then allowed tocool and stirred overnight.

[0143] The following day the reactor contents were topped on a rotaryevaporator and dichloromethane (30 ml) charged. This was also topped onthe rotary evaporator to remove residual thionyl chloride, sulphurdioxide and hydrogen chloride from the acid chloride reaction. Ayellow/brown oil was obtained (11.44 gm) which was analysed by GLC, GCMSand NMR to confirm the material was acid chloride of4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid.

[0144] Polarimetry of the acid chloride in dichlioromethane (5.78gm/litre at 20° C.) gave an ∝_(D)=+26°.

[0145] Step B

[0146] The acid chloride obtained from step A (10.19 gm-0.03 mol) wasthen run into dry methanol (30 ml) which was stirred in a clean dry 100ml reaction flask fitted with thermometer, condenser, nitrogen purge andmagnetic stirrer. The reactor contents were stirred for a further 50hours before topping off the methanol on a rotary evaporator to yield ared/brown oil (7.83 gm-0.0237 mol) which was analysed by GLC, GCMS andNMR to confirm the material was the methyl ester of4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid.

[0147] Polarimetry of the methyl ester in dichloromethane (18.17gm/litre at 20° C.) gave an ∝_(D)=+26.4°.

EXAMPLE 9 Preparation of the (+) Enantiomer of cis methyl3-(2,2-dichloro-3,3,3-trifluoropropyl)-2,2-dimethyl-cyclopropanecarboxylate

[0148] The (−) enantiomer of the methyl ester of4,6,6-trichloro-7,7,7-trifluoro-3,3-dimethylheptanoic acid (14.43 gm)was cyclised with sodium t-butoxide base (6.3 gm 100%) in t-butanol/DMFsolvent at <0° C. to produce methyl3-(2,2-dichloro-3,3,3-trifluoropropyl)-2,2-dimethyl-cyclopropanecarboxylate which was isolated by quenching with water and extractinginto dichloromethane. After washing with water and brine the product wasobtained as a yellow/orange oil (10.1 gm) by topping off thedichloromethane solvent. The product obtained was analysed by GLC, GCMSand NMR to confirm the material was consistent with that of methyl3-(2,2-dichloro-3,3,3-trifluoropropyl)-2,2-dimethyl-cyclopropanecarboxylate and it had a 80/20 cis:trans ratio.

[0149] Polarimetry of the methyl3-(2,2-dichloro-3,3,3-trifluoropropyl)-2,2-dimethyl-cyclopropanecarboxylate in dichioromethane (5.84 gm/litre at 20° C.) gave an∝_(D)=+10.3°.

EXAMPLE 10 Preparation of (+) Enantiomer of cis-Z3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethyl-cyclopropanecarboxylic acid

[0150] (+) Methyl3-(2,2-dichloro-3,3,3-trifluoropropyl)-2,2-dimethyl-cyclopropanecarboxylate cyclopropanecarboxylic (9.1 gm) was dissolved in methanolicpotassium hydroxide (3.44 gm @100%) and heated to 60° C. in a clean dry25 ml flask fitted with condenser, thermometer, nitrogen purge andmagnetic stirrer. Heat was applied from an external oil bath. After 1hour on temperature sodium carbonate (1.59 gm) was charged followed byethanol (10 ml) and the reaction temperature increased to 90° C. andheld for 8 hours to complete as judged by GLC. The product was obtainedby topping off the solvent from the reaction, adding water (50 ml) andconcentrated hydrochloric acid to adjust the pH to <2, followed bydichloromethane (50 ml). After separation a second similardichloromethane wash of the aqueous phase was applied, separated andcombined with the first wash. The combined organic layer was washed withwater, brine and then topped to give a yellow paste (5.83 gm). Theproduct obtained was analysed by HPLC, GCMS and NMR to confirm thematerial was consistent with that of structure (IIIa). HPLC revealedthat the product was a mixture of Cis and Trans isomers in the ratio of˜85:15 respectively.

[0151] Polarimetry of the air dried crude product cis-Z3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethylcyclopropanecarboxylic acid in dichloromethane (5.89 gm/litre at 20° C.) gave an∝_(D)=+24.1°.

EXAMPLE 11 Purification of cis-Z (+)3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethyl-cyclopropanecarboxylic acid

[0152] The crude acid obtained from Example 10 was recrystallised togive a product that was 100% cis-Z isomer by HPLC product (3.19 gm). Theproduct was analysed by GLC, GCMS, NMR to ensure it was consistent withthe structure of cis-Z3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethyl-cyclopropanecarboxylic acid. Polarimetry of the purified product in dichloromethane(6.312 gm/litre) gave an ∝_(D)=+46°. The rotation of cis-Z 1R (+)3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethyl-cyclopropanecarboxylic acid is given in the literature +48° (U.S. Pat. No. 4,780,252and +47° (PCT patent application No WO97/03941).

EXAMPLE 12 Preparation of cis-Z (+)3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethyl-cyclopropanecarboxylic acid chloride

[0153] A 1 litre dry, clean jacketed split reaction vessel equipped withagitator, thermometer, condenser, nitrogen blanket and vent to ascrubber system was charged with toluene (450 ml) and agitated whilstcis-Z (+)3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethyl-cyclopropanecarboxylic acid (89.4 gm=0.369 mol) was added followed by triethylamine(0.21 gm=2.1 mmol). The reaction mixture was then heated to 45° C.,using oil circulation on the jacket, and thionyl chloride (62.0 gm=0.52mol) was then charged over 105 minutes maintaining on temperature. Thereaction mass was then agitated for 5 hours at 45° C. then tested by GLCfor completion of reaction showing 2% residual acid. A further additionof thionyl chloride (4.4 gm=37 mmol) was then made and the reaction massallowed to cool with stirring overnight. The following day, residualthionyl chloride, dissolved sulphur dioxide and hydrogen chloride gaseswere removed by distillation of about 320 ml toluene under vacuum. GC,GCMS and NMR analysis of the product were consistent with the structureof the acid chloride (IIIa). Yield, 175 gm of a 54% solution of the acidchloride in toluene, ˜97% theory. α_(D)=+46°

EXAMPLE 13 Preparation of the (+) Enantiomer of tefluthrin(2,3,5,6-tetrafluoro-4-methylbenzyl-(Z)-(1RS)-cis-3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethylcyclopropanecarboxylate

[0154] Step A

[0155] A 100 ml 3-necked round bottom flask was equipped with a stirrerbar, thermometer, PTFE syringe needle, reflux condenser, N₂ sparge andwas vented to a caustic scrubber. To the reactor was charged (+) 1Rcis-Z 3-(2-chloro-3,3,3-trifluoro-1-propenyl)-2,2-dimethylcyclopropanecarboxylic acid chloride ((IIIa) [20.76 g (ca.54% w/w toluene solution),43 mmol], then the acid chloride solution was heated to 42° C. withagitation. 2,3,5,6-Tetrafluoro-4-methylbenzyl alcohol (7.2 g, 37 mmol)in toluene (14 ml) was added to the reactor over 3 hr (via. syringepump). The reaction was agitated at 25-42° C. for 4 days, thenadditional charges of the alcohol were made (total 1.6 g, 8.2 mmol). Thereaction was then heated to 95° C. for 7 hr before cooling to roomtemperature.

[0156] Step B

[0157] The reaction mass was distilled under vacuum (100° C./10 mbar) toremove toluene. The product was a mid-brown oil (15.0 g, 80% yield, andwhen taking into account samples removed for analysis, the yield wasabout 95% of the (+) enantiomer of tefluthrin(2,3,5,6-tetrafluoro-4-methylbenzyl-(Z)-(1RS)-cis-3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethylcyclopropanecarboxylate.

[0158] GC/MS: 225, 197, 177, 141, 127, 101, 91

[0159] 1H NMR (CDCl3): δ1.3 (s, 6H, geminal CH3), 2.0 (d, 1Hcyclopropane ring), 2.15 (d, 1H cyclopropane ring), 2.3 (s, 3H, ArCH3),5.2 (d, 2H, ArCH2O), 6.9 (d, 1H, CF3ClC═CH) The optical rotation of theproduct was measured in dichloromethane at 20° C. (5.56 g/litre) givingan ∝_(D)=+17°.

1. A process for producing compounds of formula (VIIa) and (VIIb)

wherein X is a leaving group; Y and Y¹ are independently Cl or Br; and Zis Cl, Br or a haloalkyl group which process comprises a) reacting acompound of formula (VII)

wherein X, Y, Y¹ and Z are as defined for compounds (VIIa) and (VIIb)with a substantially optically pure chiral amine in a solvent to form adiastereoisomeric salt; b) separating the diastereomeric salt of eachenantiomer; c) converting the diastereomeric salt of each enantiomerseparately to compounds of formulae (VIIa) and (VIIb) respectively byacid or base hydrolysis.
 2. A process according to claim 1 wherein X isCl or Br.
 3. A process according to claim 1 or claim 2 wherein Y and Y¹are both Cl and Z is CF₃.
 4. A process for preparing an enantiomer of acompound of formula (III)

or an enantiomerically enriched compound of formula (III) wherein Y andZ are as defined in relation to formula (VII) in claim 1 comprising a)preparing an enantiomer of a compound of formula VII or anenantiomerically enriched compound of formula VII according to claim 1;b) converting the product from step a) to give a single enantiomer orenantiomerically enriched compound of formula (VI)

wherein X, Y, Y¹ and Z are as defined in relation to formula (VII) inclaim 1 by chlorination; c) esterifying the product of step b) to give asingle enantiomer or enantiomerically enriched compound of formula (V)

wherein X, Y, Y¹ and Z are as defined in relation to formula (VII) inclaim 1 and R is alkyl; d) cyclising the product of step c) to give asingle enantiomer or enantiomerically enriched compound of formula (IV)

wherein Y, Y¹ and Z are as defined in relation to formula (VII) in claim1 and R is alkyl; and e) converting the product of step d) to a singleenantiomer or enantiomerically enriched compound of formula (III) byhydrolysis and dehydrochlorination.
 5. A process for preparing anenantiomer of a compound of formula (I)

or an enantiomerically enriched compound of formula (I) where Y and Zare as defined for formula (VII) in claim 1 and E is an insecticidallyactive ester moiety comprising a) preparing an enantiomer of a compoundof formula III or an enantiomerically enriched compound of formula IIIaccording to claim 4; b) chlorinating the product of step a) to give asingle enantiomer or enantiomerically enriched compound of formula (II)

where Y and Z are as defined in relation to formula (VII) in claim 1;and c) esterifying the product of step b) to give a single enantiomer orenantiomerically enriched compound of formula (I).
 6. A processaccording to claim 5 wherein E is derived from 4-alkyltetrafluorobenzylalcohols (especially 4-methyltetrafluorobenzyl alcohol),4-alkoxytetrafluorobenzyl alcohols, α-cyano-3-phenoxybenzyl alcohol,3-phenoxybenzyl alcohol or 2-methyl-3-phenylbenzyl alcohol.
 7. The (−)enantiomer of a compound of formula (VII), formula (VI) or formula (V)or salts thereof:

wherein R is H or alkyl and X, Y, Y¹ and Z are as defined in relation toformula (VII) in claim
 1. 8. The (+) enantiomer of a compound of formula(VII), formula (VI) or formula (V) or salts thereof:

wherein R is H or alkyl and X, Y, Y¹ and Z are as defined in relation toformula (VII) in claim
 1. 9. The (−) enantiomer of a compound of formula(IV) or salts thereof:

wherein R is H or alkyl and Y, Y¹ and Z are Cl or Br.
 10. The (+)enantiomer of a compound of formula (IV) or salts thereof:

wherein R is H or alkyl and Y, Y¹ and Z are Cl or Br.
 11. The (+)enantiomer of(2,3,5,6-tetrafluoro-4-methylbenzyl-(Z)-(1RS)-cis-3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethylcyclopropanecarboxylate.12. An insecticidal acaricidal and nematicidal composition comprising aninsecticidally, acaricidally or nematicidally effective amount of the(+) enantiomer of(2,3,5,6-tetrafluoro-4-methylbenzyl-(Z)-(1RS)-cis-3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethylcyclopropanecarboxylate.13. A method of combating and controlling acarine or nematode pests at alocus which comprises treating the pests or the locus of the pests withan effective amount of the (+) enantiomer of(2,3,5,6-tetrafluoro-4-methylbenzyl-(Z)-(1RS)-cis-3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethylcyclopropanecarboxylate.